Bipolar disorder is a severe, persistent, and common psychiatric illness that is associated with a staggering 46% lifetime prevalence of alcohol-related disorders. When present in patients with bipolar disorder, alcohol dependence is associated with numerous adverse consequences including increased hospitalization, poor outcome during hospitalization, violence towards self and others, and treatment nonadherence. Thus, effective treatment of patients with bipolar and alcohol dependence is a major public health concern. However, to date, only one placebo-controlled trial has been reported in patients with bipolar disorder and alcohol dependence. Our group over the past 8 years has developed a research program that conducts clinical trials in persons with bipolar disorder and substance-related disorders. One particularly promising medication that we have investigated is the atypical antipsychotic quetiapine. Both open-label and placebo-controlled pilot data from our group suggest that quetiapine add-on therapy is well tolerated and associated with a reduction in alcohol use and improvement in mood in patients with bipolar disorder and alcohol dependence. A 12-week randomized, double-blind, placebo-controlled, study of quetiapine add-on therapy in 86 outpatients with bipolar I or II disorder, depressed phase and alcohol dependence with active alcohol use is proposed. To reflect the diversity of our geographic region, both English- and Spanish-speaking participants will be included. Each participant will also receive a psychosocial platform of manual-driven cognitive behavioral therapy specifically designed for patients with bipolar disorder and substance dependence. Outcome measures will include alcohol use assessedwith the Timeline Followback method, Hamilton Rating Scale for Depression, Inventory of Depressive Symptomatology-Self-report, Young Mania Rating Scale, Penn Alcohol Craving Scale, and liver enzymes. Side effects will be monitored. To standardize management of concomitant medications (e.g., mood stabilizers, antidepressants), concomitant medication changes, when absolutely necessary, will be managed in both groups using a treatment algorithm. Alcohol use will be the primary outcome, with alcohol craving and mood symptoms as secondary outcomes. The relationship between changes in alcohol use and changes in mood will be explored. A research team with extensive experience in dual diagnosis, mood disorders, clinical trials, statistics, and alcohol dependence research has been assembled to conduct the trial.